A novel mechanism of eukaryotic translation initiation that is neither m7G-cap-, nor IRES-dependent
Resistance of translation of some eukaryotic messenger RNAs (mRNAs) to inactivation of the cap-binding factor eIF4E under unfavorable conditions is well documented. To date, it is the mechanism of internal ribosome entry that is predominantly thought to underlay this stress tolerance. However, many...
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| Format: | Online |
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Oxford University Press
2013
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3561988/ |
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pubmed-35619882013-02-01 A novel mechanism of eukaryotic translation initiation that is neither m7G-cap-, nor IRES-dependent Terenin, Ilya M. Andreev, Dmitri E. Dmitriev, Sergey E. Shatsky, Ivan N. Molecular Biology Resistance of translation of some eukaryotic messenger RNAs (mRNAs) to inactivation of the cap-binding factor eIF4E under unfavorable conditions is well documented. To date, it is the mechanism of internal ribosome entry that is predominantly thought to underlay this stress tolerance. However, many cellular mRNAs that had been considered to contain internal ribosome entry sites (IRESs) failed to pass stringent control tests for internal initiation, thus raising the question of how they are translated under stress conditions. Here, we show that inserting an eIF4G-binding element from a virus IRES into 5′-UTRs of strongly cap-dependent mRNAs dramatically reduces their requirement for the 5′-terminal m7G-cap, though such cap-independent translation remains dependent on a vacant 5′-terminus of these mRNAs. Importantly, direct binding of eIF4G to the 5′-UTR of mRNA makes its translation resistant to eIF4F inactivation both in vitro and in vivo. These data may substantiate a new paradigm of translational control under stress to complement IRES-driven mechanism of translation. Oxford University Press 2013-02 2012-12-24 /pmc/articles/PMC3561988/ /pubmed/23268449 http://dx.doi.org/10.1093/nar/gks1282 Text en © The Author(s) 2012. Published by Oxford University Press. http://creativecommons.org/licenses/by-nc/3.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc/3.0/), which permits non-commercial reuse, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com. |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Terenin, Ilya M. Andreev, Dmitri E. Dmitriev, Sergey E. Shatsky, Ivan N. |
| spellingShingle |
Terenin, Ilya M. Andreev, Dmitri E. Dmitriev, Sergey E. Shatsky, Ivan N. A novel mechanism of eukaryotic translation initiation that is neither m7G-cap-, nor IRES-dependent |
| author_facet |
Terenin, Ilya M. Andreev, Dmitri E. Dmitriev, Sergey E. Shatsky, Ivan N. |
| author_sort |
Terenin, Ilya M. |
| title |
A novel mechanism of eukaryotic translation initiation that is neither m7G-cap-, nor IRES-dependent |
| title_short |
A novel mechanism of eukaryotic translation initiation that is neither m7G-cap-, nor IRES-dependent |
| title_full |
A novel mechanism of eukaryotic translation initiation that is neither m7G-cap-, nor IRES-dependent |
| title_fullStr |
A novel mechanism of eukaryotic translation initiation that is neither m7G-cap-, nor IRES-dependent |
| title_full_unstemmed |
A novel mechanism of eukaryotic translation initiation that is neither m7G-cap-, nor IRES-dependent |
| title_sort |
novel mechanism of eukaryotic translation initiation that is neither m7g-cap-, nor ires-dependent |
| description |
Resistance of translation of some eukaryotic messenger RNAs (mRNAs) to inactivation of the cap-binding factor eIF4E under unfavorable conditions is well documented. To date, it is the mechanism of internal ribosome entry that is predominantly thought to underlay this stress tolerance. However, many cellular mRNAs that had been considered to contain internal ribosome entry sites (IRESs) failed to pass stringent control tests for internal initiation, thus raising the question of how they are translated under stress conditions. Here, we show that inserting an eIF4G-binding element from a virus IRES into 5′-UTRs of strongly cap-dependent mRNAs dramatically reduces their requirement for the 5′-terminal m7G-cap, though such cap-independent translation remains dependent on a vacant 5′-terminus of these mRNAs. Importantly, direct binding of eIF4G to the 5′-UTR of mRNA makes its translation resistant to eIF4F inactivation both in vitro and in vivo. These data may substantiate a new paradigm of translational control under stress to complement IRES-driven mechanism of translation. |
| publisher |
Oxford University Press |
| publishDate |
2013 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3561988/ |
| _version_ |
1611951952390782976 |